Expression of N-methyl-D-aspartate receptor subunits and induction of c-fos in otolith neurons in the vestibular nuclei of postnatal rats

Abstract

The developmental profile of functionally activated otolith neurons within the vestibular nucleus was examined in conscious young (P7-P28) and adult SD rats. Neuronal activation was defined by the expression of c-fos mRNA and/or Fos protein in response to constant velocity off-vertical axis rotation (OVAR), a stimulus that selectively activates otolith receptors. Labyrinthectomized rats subjected to OVAR showed only a few sporadically scattered labeled neurons. The pattern of c-fos expression in normal experimental rats was thus due to otolith activation. At P7, the number of Fos-positive vestibular nuclear neurons was small, contrasting those found in adults. This indicates that functional connection between central otolith neurons and peripheral receptors is established as early as P7. From P7 to P14, the number of Fos-positive vestibular nuclear neurons increased significantly and reached adult levels at P21. The cellular localization of NMDA receptor subunits in vestibular nuclei was also immunohistochemically examined. At P7, some OVAR-activated Fos-positive neurons expressed NMDA receptor subunits, indicating an early activation of glutaminergic central otolith neurons. The proportion of either NR1-Fos or NR2A/B-Fos double-labeled neurons progressively increased from P7 to adult, while the proportion of NR2C-Fos double-labeled neurons reached a maximum at P14. Our findings suggest that changes in the expression of NMDA receptor subunits in the first two postnatal weeks contribute to the mechanism of maturation in central otolith neurons.